Studies on agents with vasodilator and beta-blocking activities. V. Synthesis and pharmacological activity of the optical isomers of TZC-5665.
Synthesis of the four optical isomers of TZC-5665 (1), a candidate for the treatment of congestive heart failure, was achieved by the reaction of chiral diaminopyridazinone (2) with chiral glycidyl ether. (3). The hypotensive and beta-blocking activities of 1 and its optical isomers were examined when given intravenously into anesthetized rats. Furthermore these compounds were evaluated for inhibitory activity on cAMP phosphodiesterase III. Among the four optical isomers, Ra,Sb-one (1c) possessed the essential activities of TZC-5665 (1).
Seki
T
T
Research Division, Teikoku Hormone Manufacturing Co., Ltd., Kanagawa, Japan.
Kanada
A
A
Nakao
T
T
Shiraiwa
M
M
Asano
H
H
Miyazawa
K
K
Ishimori
T
T
Minami
N
N
Shibata
K
K
Yasuda
K
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000737:chemistry; D006333:Heart Failure / Q000188:drug therapy; D007275:Injections, Intravenous; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D011724:Pyridazines; D014665:Vasodilator Agents; C020344:glycidyl ethers; C088090:TZC 5665; D015105:3',5'-Cyclic-AMP Phosphodiesterases